Adjuvants have extensive use in immunotherapy. The majority of cellular based immunotherapies administer adjuvants prior to giving antigen specific treatment. Typically these antigens include GM-CSF, IL-1, QP-100, Keyhole Limpet Cynanin, and others. These adjuvants are typically administered systemically via IV, IM, ID or similar routes.
Listeria monocytogenes (Lm) is an intracellular pathogen that primarily infects antigen presenting cells and has adapted for life in the cytoplasm of these cells. Listeria monocytogenes and a protein it produces named listeriolysin O (LLO) have strong adjuvant properties, that unlike the majority of adjuvants used for cellular based immunotherapies, can be administered after providing an antigen specific treatment.
A method of rapidly elevating a subject's immune response to any antigen is needed in order to decrease disease frequency in the subject and mortality resulting thereof. The present invention provides methods of elevating an immune response in subjects such as human adults and children by taking advantage of the adjuvant properties provided by live Lm vaccines that secrete non-hemolytic LLO or a truncated ActA.
Further, the same method is provided to reconstitute the immune response or facilitate the recovery of an immune response to normal or approximately normal levels in subjects that have undergone cytotoxic treatment as a result of cancer.